Multifocal PNI is associated with poor outcomes even with PORT suggesting consideration of therapeutic escalation, particularly with involved nerves ≥1 mm. Unifocal PNI did not affect prognosis even in the absence of PORT, which may not be required if this is the sole risk factor. Prospective validation and testing of these hypotheses is essential before implementation.

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IMPORTANCEAlthough regression is commonly observed in cutaneous melanoma, it is uncertain whether it is associated with patient prognosis. OBJECTIVE To determine whether histologically confirmed regression was associated with better or worse survival in patients with primary cutaneous melanoma. DESIGN, SETTING, AND PARTICIPANTSThis cohort study analyzed data from 2 large cohorts of adults (one in the Netherlands and the other in Australia) with histologically proven, stage 1 and 2 primary, invasive cutaneous melanoma with known regression status treated between 2000 and 2014, with median follow-up times of 4.5 and 11.1 years for the Dutch and Australian cohorts, respectively. For the Dutch patients, population-based data from PALGA, the Dutch Pathology Registry, were used, and follow-up data were retrieved from the Netherlands Cancer Registry. For the Australian patients, data from the database of a large, specialized melanoma treatment center were used.MAIN OUTCOMES AND MEASURES Multivariable Cox proportional hazards analyses were performed per cohort to assess recurrence-free survival (RFS) and overall survival (OS), and subgroup analyses according to Breslow thickness category and melanoma subtype were performed.RESULTS A total of 17 271 Dutch patients and 4980 Australian patients were included. In both cohorts, survival outcomes were better for patients with disease regression. For Dutch patients, the hazard ratio (HR) for those with disease regression was 0.55 (95% CI, 0.48-0.63; P < .001) for RFS and 0.87 (95% CI, 0.79-0.96; P = .004) for OS; for the Australian patients, the HR was 0.61 (95% CI, 0.52-0.72; P < .001) for RFS and 0.73 (95% CI, 0.64-0.84; P < .001) for OS. Subgroup analyses showed that the presence of regression improved RFS within thin and intermediate Breslow thickness melanomas in both cohorts. For patients with superficial spreading melanoma (SSM) subtype, regression improved RFS and OS in both cohorts. For Dutch patients with SSM, the HR for those with disease regression was 0.54 (95% CI, 0.46-0.63; P < .001) for RFS and 0.86 (95% CI, 0.76-0.96; P = .009) for OS; for the Australian patients with SSM, the HR was 0.67 (95% CI, 0.52-0.85; P = .001) for RFS and 0.72 (95% CI, 0.59-0.88; P = .001) for OS. CONCLUSIONS AND RELEVANCEIn 2 large patient cohorts from 2 different continents, regression was a favorable prognostic factor for patients with stage 1 and 2 melanomas, especially in those with thin and intermediate thickness tumors and those with SSM subtype.

The structure of Ba(3)BaSb(2)O(9) is reported for the first time as a high-temperature phase with an ideal hexagonal BaTiO(3)-type structure (space group P6(3)/mmc) and Rietveld-refined against high-temperature synchrotron X-ray powder diffraction data. The structure is remarkable for the extreme size difference between the pairs of face-sharing Sb(5+)O(6) octahedra (with mean Sb-O bonds of 1.99 Angstroms) and the single corner-sharing Ba(2+)O(6) octahedra (with mean Ba-O bonds of 2.46 Angstrom), which is greater than for any other reported 6H perovskite. This is consistent with the very different ionic radii of Sb(5+) (0.60 Angstroms) and Ba(2+) (1.35 Angstroms), and accounts for the instability of this phase at room temperature. The known symmetry-lowering modes of closely related 6H perovskites such as Ba(3)SrNb(2)O(9) and Ba(3)SrTa(2)O(9) are considered, but found not to account for the behaviour of Ba(3)BaSb(2)O(9) on cooling from high temperatures.

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Our study demonstrated imprecision in Breslow thickness measurements and its significant impact on staging. Two potential sources of imprecision are failure to follow standardized thickness measurement guidelines and the phenomenon of terminal digit bias, not previously identified as a problem in this field. Educating pathologists about this phenomenon and the importance of utilizing ocular micrometers may improve the precision of melanoma thickness measurements around critical staging cut-off points. Clinicians must also be educated to appreciate that there is an inevitable margin of error with Breslow thickness measurements that should be considered when making management decisions.